Conserved Partial Reprogramming Effects on the Methylome

Background/Objectives: Among the many proposed theories of aging, a growing body of research points to epigenetic alterations, particularly changes in DNA methylation patterns, as key contributors to biological decline. DNA methylation can be targeted and modulated to induce anti-aging and regenerative effects using an emerging therapeutic approach known as partial reprogramming, induced by different combinations of Yamanaka factors. Methods: In this study, we performed an integrative secondary analysis of five publicly available DNA methylation datasets derived from partial reprogramming experiments across multiple mammalian species, tissues, cell types and combinations of transcription factors (n = 189 samples). Results: Following differential methylation analysis of 929,009 CpGs, we identified 14 CpG sites showing reproducible and significant changes, with two CpGs consistently present across all datasets. Conclusions: These findings suggest that partial reprogramming may exert anti-aging and regenerative effects, in part, through the selective modulation of conserved DNA methylation sites.